What Is Clazakizumab?
Clazakizumab is a type of medication known as a monoclonal antibody. Specifically, it is an anti-interleukin-6 (anti-IL-6) monoclonal antibody. Interleukin-6 (IL-6) is a protein in the body that plays a key role in inflammation and immune responses. By targeting and blocking IL-6, Clazakizumab aims to reduce excessive inflammation and modulate the immune system, which can be beneficial in various diseases.
Currently, Clazakizumab is being investigated in clinical trials for a range of conditions where inflammation or immune system dysregulation plays a significant role. These include conditions related to kidney transplantation, such as antibody-mediated rejection and transplant glomerulopathy, as well as other inflammatory conditions like rheumatoid arthritis. It has also been studied for its potential role in treating COVID-19. A total of 11 clinical trials have been conducted or are ongoing to evaluate its safety and effectiveness, involving 1,622 participants since the first trial began in 2013.
Uses and Conditions Under Study
Clazakizumab is being studied for its potential to treat several conditions, primarily focusing on kidney-related issues and broader inflammatory responses. The drug's mechanism of blocking IL-6 suggests it could help in conditions where inflammation and immune system overactivity contribute to disease progression.
- Kidney Transplant and Rejection: A significant focus of research for Clazakizumab is in conditions affecting kidney transplant recipients. This includes antibody-mediated rejection, which has been studied in 4 trials, and transplant glomerulopathy, investigated in 2 trials. It is also being explored for general kidney transplant complications (2 trials), kidney transplant failure and rejection (1 trial), and kidney transplant rejection (1 trial). By modulating the immune response, Clazakizumab may help prevent or treat rejection of transplanted kidneys and improve long-term outcomes for patients.
- Inflammatory Conditions: Beyond transplantation, Clazakizumab has been investigated for its effects on general inflammation and specific autoimmune diseases. One trial has explored its use in rheumatoid arthritis, a chronic inflammatory disorder primarily affecting joints. Another trial focused on broader inflammation. The drug's ability to inhibit IL-6 makes it a candidate for reducing the systemic inflammation seen in these conditions.
- COVID-19: Given the severe inflammatory response observed in some patients with COVID-19, Clazakizumab was studied in 3 trials for its potential to mitigate the cytokine storm and reduce inflammation associated with the viral infection. This research aimed to see if blocking IL-6 could improve outcomes for patients experiencing severe COVID-19 symptoms.
- Other Conditions: Clazakizumab has also been explored in single trials for chronic kidney failure and frailty. These studies aim to understand if reducing inflammation through IL-6 inhibition could offer benefits in these complex health challenges.
Dosing
Clazakizumab has been studied in various dosage forms and administration routes in clinical trials. The primary forms investigated are injectable solutions, administered either intravenously (IV) or subcutaneously.
For intravenous administration, doses of 25 mg have been studied. This typically involves an infusion administered over 30 minutes. One trial description noted that the first dose would be given as soon as possible after enrollment and randomization into the 25 mg arm, with serum C-reactive protein (CRP) evaluated to monitor the inflammatory response.
A subcutaneous injection form has also been investigated, with a dose of 5 mg administered every 4 weeks for a duration of 24 weeks. Other strengths, such as 12.5 mg, have also been part of investigational arms in clinical trials, often in a double-blind setting comparing different doses or against a placebo.
It is important to note that specific dosing regimens, including frequency and duration, are determined by the particular clinical trial protocol and the condition being studied. The data provided does not specify distinct pediatric dosing, focusing instead on adult investigational uses.
Side Effects
In clinical trials, the most common side effects reported with Clazakizumab varied depending on the study population and dose. In one trial involving 104 patients, hypotension (low blood pressure) was reported in 38.5% of patients taking Clazakizumab, compared to 56.8% on placebo. Fever was also reported in 38.5% of patients on Clazakizumab, compared to 79.7% on placebo in this same trial. In studies involving larger patient groups (up to 1,97 patients), anemia was observed in 22.3% of patients on Clazakizumab, compared to 27.6% on placebo.
Other common side effects observed in larger trials (up to 1,846 patients) included:
- Upper respiratory tract infection: 4.7% of patients taking Clazakizumab experienced this, compared to 11.1% on placebo.
- Diarrhea: 3.7% of patients on Clazakizumab, compared to 6.9% on placebo.
- Sinusitis: 3.6% of patients on Clazakizumab, compared to 5.7% on placebo.
- Nausea: 3.4% of patients on Clazakizumab, compared to 4.3% on placebo.
- Nasopharyngitis (common cold): 2.7% of patients on Clazakizumab, compared to 8.8% on placebo.
- Cough: 2.7% of patients on Clazakizumab, compared to 4.9% on placebo.
- Headache: 2.7% of patients on Clazakizumab, compared to 5.1% on placebo.
Clinical Trial Results
Rheumatoid Arthritis
In a Phase IIB dose-ranging study (NCT02015520) for moderate to severe rheumatoid arthritis, Clazakizumab was studied in combination with methotrexate (MTX). At Week 12, patients receiving Clazakizumab 5 mg + MTX showed an American College of Rheumatology (ACR) 20% improvement rate of 50.0%, compared to 7.5% for placebo + MTX. For ACR 50% improvement, Clazakizumab 25 mg + MTX showed a 47.5% response rate, compared to 2.5% for placebo + MTX.
Regarding disease activity, the mean change from baseline in the Clinical Disease Activity Index (CDAI) score at Week 12 was -21.6 for Clazakizumab 25 mg + MTX, indicating greater improvement compared to -9.9 for placebo + MTX. Similarly, the mean change in Disease Activity Score in 28 Joints - C-reactive Protein (DAS28-CRP) was -2.43 for Clazakizumab 25 mg + MTX, versus -0.75 for placebo + MTX. A higher percentage of patients achieved DAS28-CRP remission (score <2.6) with Clazakizumab: 15.0% for the 25 mg dose and 14.3% for the 5 mg dose, compared to 5.0% for placebo.
Chronic Active Antibody Mediated Rejection in Kidney Transplant Recipients
Two studies investigated Clazakizumab for chronic active antibody mediated rejection (cABMR) after kidney transplant. In a study (NCT03380377) without a placebo arm, 7 participants experienced donor-specific antibody (DSA) elimination or reduction, and 9 participants showed stabilization of clinical features of cABMR based on BANFF biopsy grading criteria. The mean estimated glomerular filtration rate (eGFR) was 41.6 ml/min/1.73m2.
A larger study (NCT03744910) compared Clazakizumab to placebo. The mean change from baseline to Week 52 in eGFR showed a decline of -8.0 ml/min/1.73m2 for Clazakizumab, compared to -5.2 ml/min/1.73m2 for placebo. The incidence of acute rejection episodes was 2 participants (2.2%) in the Clazakizumab arm (out of 90) versus 3 participants (3.1%) in the placebo arm (out of 98). However, the percentage of participants with composite all-cause allograft loss or irreversible loss of allograft function was 28.3% for Clazakizumab, compared to 22.2% for placebo.
Life-threatening COVID-19 Infection
In a randomized, placebo-controlled study (NCT04343989) for patients with life-threatening COVID-19, Clazakizumab was evaluated for safety and dose-finding. The number of serious adverse events was lower in the Clazakizumab arms: 6 for the 12.5 mg dose (30% of 20 participants) and 46 for the 25 mg dose (76.7% of 60 participants), compared to 51 for placebo (94.4% of 54 participants).
Overall patient survival was higher with Clazakizumab: 100% (20 out of 20 participants) for the 12.5 mg dose and 93.3% (56 out of 60 participants) for the 25 mg dose, compared to 85.2% (46 out of 54 participants) for placebo. Ventilator-free survival was also higher in the Clazakizumab groups: 95% (19 out of 20 participants) for the 12.5 mg dose and 96.7% (58 out of 60 participants) for the 25 mg dose, compared to 81.5% (44 out of 54 participants) for placebo.
Severe and/or Exacerbation-Prone Asthma
In the PrecISE Network Study (NCT04129931), Clazakizumab was compared to placebo for severe asthma. Patients on Clazakizumab experienced a mean of 1.3 CompEx events per year, compared to 1.4 events per year for placebo. The mean number of asthma exacerbations per year was 0.55 for Clazakizumab, versus 0.64 for placebo.
Currently Recruiting Trials
Currently, there are no clinical trials for Clazakizumab actively seeking new participants. This means that if you are interested in joining a study for this investigational medication, you would need to monitor for future trial announcements. Clinical trials are essential for evaluating new treatments, and their availability can change as studies complete enrollment or new ones begin.Where to Participate
As there are no Clazakizumab trials currently recruiting, there are no specific sites, cities, or states where participation is possible at this time. However, generally, Clazakizumab trials have been designed for all genders, and they do not typically enroll healthy volunteers or children. Eligibility for future studies would likely focus on individuals with specific medical conditions relevant to the drug's development.Development Timeline
The journey of Clazakizumab in clinical development began on December 19, 2013, with its first recorded trial. Since then, the drug has been investigated in a total of 11 clinical trials, involving approximately 1,622 participants, with the latest trial starting on February 14, 2023. Early development saw Clazakizumab explored for conditions such as IBS-C and hyperphosphatemia. Over time, the scope of research significantly broadened. The majority of studies, eight, have been conducted in Phase 2, with two trials combining Phase 1 and Phase 2, and one reaching Phase 3. A diverse group of sponsors has driven this research, including CSL Behring, Stanley Jordan, MD, Columbia University, and Cedars-Sinai Medical Center, among others. The pipeline expanded to investigate Clazakizumab across a wide range of conditions, demonstrating its potential in various areas:- Transplant Glomerulopathy
- Kidney Transplant; Complications
- Frailty
- Inflammation
- Kidney Failure, Chronic
- Kidney Transplant Failure and Rejection
- Kidney Transplant Rejection
- Rheumatoid Arthritis
- Transplant Glomerulopathy - Early Form
- Transplant Glomerulopathy - Late Form
- Transplant;Failure,Kidney
- Asthma
- COVID-19 Infection
- End-Stage Renal Disease